tbuckley/cabot-search huggingface dataset:
Abstract 11714: High-Output Heart Failure in Multiple Myeloma: Novel Approach to a Challenging Diagnosis
Authors: Eric Hirsch, Leandro Slipczuk Bustamante, Mark Travin, Renee Moadel, Ulrich P Jorde, Sasha VUKELIC
Journal: Circulation (2022)

High-output heart failure (HOHF) is a rare complication of multiple myeloma and is believed to be related to arteriovenous shunting in osseous myeloma lesions. Timely diagnosis is crucial, as these patients respond best to aggressive treatment of the underlying malignancy. In this case, a 51-year-old man with multiple myeloma complicated by extensive osseous disease was admitted from oncology clinic for several weeks of worsening dyspnea, early satiety, and bilateral leg swelling. His exam was notable for signs of volume overload, and the BNP was elevated to 1444 pg/ml. An echocardiogram showed new right ventricular dysfunction. After the patient failed to respond to escalating doses of intravenous diuretics, right heart catheterization was performed and revealed elevated biventricular filling pressures with evidence of high cardiac output (Fick CO 17.1 LPM, Fick CI 7.9 LPM/m 2 ). In a novel diagnostic approach, 5.1 mCi of technetium-99m-labeled macroaggregated albumin was injected into the aorta at the time of left heart catheterization and then whole body planar images were obtained in anterior and posterior projections. The scan revealed evidence of lower extremity arteriovenous shunting with a proportion of 6% (Fig. 1). He was started on lenalidomide and pulse-dose dexamethasone with improvement in diuretic response and resolution of heart failure symptoms. A follow-up echocardiogram showed normalization of right ventricular size and function. He eventually underwent successful allogeneic stem cell transplant during the admission. Although Tc-99m MAA is routinely used in the diagnosis of hepatopulmonary syndrome, this is, to our knowledge, the first report of its use to investigate myeloma-related HOHF in the clinical setting. This technique was previously utilized successfully to experimentally correlate between shunting values and cardiac indices. It may be of use in a wider population of patients with HOHF in whom occult shunting is suspected.
Abstract 13269: Effects of Nicotine-Containing Product Challenges on Interleukin-6 Pathway Expression in Human Pluripotent-Derived Arterial Endothelial Cells: The Clues Study
Authors: Matthew C Tattersall, Stephane Esnault, Ron Stewart, Scott Swanson, John Steill, Claudia E Korcarz, Kristin M Hansen, Timothy B Baker, James H Stein
Journal: Circulation (2022)

Background: Electronic nicotine delivery devices (ENDs) induce interleukin-6 (IL-6) pathway expression in airway epithelial cells, but their systemic effects on arterial endothelial cells (AECs) are unknown. We hypothesized differential expression (DE) of IL-6 pathway genes by human pluripotent-derived AECs exposed in vitro to participant serum drawn before and after use of ENDS by chronic vapers, use of combustible cigarettes by smokers, and no product use by controls. Methods: For this pilot study, we randomly selected 30 participants from the CLUES Study: 10 exclusive vapers (exhaled carbon monoxide [CO] &lt;5 ppm, + urine NicCheck I), 10 exclusive smokers (CO &gt;5 ppm, + urine), and 10 non-vaping/non-smoking controls (CO &lt;5 ppm, negative urine). We generated purified populations of AECs (H9 CPTC C13 derivative human embryonic stem cell line) and exposed them for 6 hours to 50% concentrated participant serum drawn before and 15’ after a product use challenge. Total RNA was sequenced on a NextSeq 2000. The DESeq2 suite characterized DE with an a priori focus on genes in the IL-6 biosynthetic pathway gene ontology set. Z scores of normalized log2 gene expression values were determined and expressed as heat maps (Figure). Gene Set Variational Analysis (GSVA) was used to interrogate for enriched gene sets. P values were not adjusted for multiple hypothesis testing and are exploratory. Results: Vapers were a mean (SD) 28.9 (8.1) years old (30% female), smokers were 38.3 (11.6) years old (40% female), and controls were 33.6 (17.7) years old (50% female). Compared to controls, vapers had increased expression of the IL-6 pathway at baseline (p=0.004), but smokers did not (p=0.38). Following product use, vapers (p=0.0009) but not smokers (p=0.79) had increased expression of genes in the IL-6 biosynthetic pathway (Figure). Conclusion: Chronic vapers, but not smokers, may have increased expression of genes in the IL-6 pathway prior to product use with further increases afterwards.
Abstract 12704: Race And Quality of Life Among Patients With Heart Failure—A Serial Multiple Mediator Model
Authors: Jiarong Wu, Debra K Moser, Chin-Yen Lin, Ambrose A Chiang, Barbara J Riegel
Journal: Circulation (2022)

BACKGROUND: Black patients have worse quality of life than Whites. Depression and sleep quality are associated with quality of life (QoL). However, the manner in which depression and sleep quality influence the relationship between race and QoL in patients with HF is unclear. Objective: To explore whether depressive symptoms and/or sleep quality mediate the relationship between race and QoL among patients with HF. METHOD: We performed a secondary analysis of data from 271 adults with HF in this descriptive study. Participants were enrolled from out-patient settings in the Northeastern US. Self-reported race (White or Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected at baseline. A serial multiple mediator analysis was conducted with a regression framework, using the PROCESS macro for SPSS. Results: Ninety-six patients (35.4%) were Black. Race was directly associated with depressive symptoms and sleep quality. Black patients had more depressive symptoms and poorer sleep quality than White patients. Depressive symptoms were directly associated with sleep quality and QoL. Sleep quality was directly associated with QoL. Race was not directly associated with QoL; but indirectly associated with QoL through the following three paths: 1) depressive symptoms; 2) sleep quality; 3) depressive symptoms and sleep quality. Due to more depressive symptoms and/or poorer sleep quality, Black patients had poorer QoL than Whites (Figure). Conclusion: Depressive symptoms and sleep quality independently and in combination mediated the relationship between race and QoL. These findings suggest that screening for depressive symptoms and sleep quality could identify patients at risk for poor QoL, especially in racial minority groups.
Abstract 12551: Self-Monitoring of Blood Pressure and Feedback Using App in Treatment of Uncontrolled Hypertension: SMART-BP Study
Authors: MINJAE YOON, Dong Choi
Journal: Circulation (2022)

Introduction: Self-monitoring of blood pressure (SMBP) is a reliable method used to assess blood pressure (BP) accurately. However, patients do not often know how to respond to the measured BP value. We developed a mobile application-based feedback for tailored recommendations and aimed to evaluate whether this feedback is superior to SMBP alone in terms of BP reduction and drug compliance improvement in patients with hypertension. Methods: Self-Monitoring of and Feed-back using APP in TReatment of UnconTrolled Blood Pressure (SMART-BP) is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App compared with SMBP alone. In the SMBP alone group, the patients performed home BP measurement and receive the standard care, whereas in the SMBP-App group, the patients received additional recommendations from the application using feedback algorithm in response to the obtained BP value. The primary endpoints were mean home BP and adherence of antihypertensive medication. Follow-up visits were scheduled at 12 and 24 weeks after randomization. Results: Among total 173 patients (88 for SBMP-App and 85 for SMBP alone) with full-analysis set, 53% were men, and mean age was 59.8 years. Baseline characteristics including BP were not significantly different between the two groups. At 24 weeks, mean reduction in home systolic BP was significantly higher in SMBP-App group than SBMP alone group (-22.4±13.5 vs. -17.2±13.3, P=0.019). Also, SMBP-App group showed higher drug adherence value and proportion of ≥95% adherence than in SMBP alone group (100% [97.2%-100.0%] vs. 97.6% [94.0%-100.0%], P=0.025; 86.1% vs. 68.0%, P=0.013). Reduction in home systolic BP at 12 weeks and office systolic BP at 12 or 24 weeks were also higher in SBMP-App, similar with primary end point. Conclusions: SMBP-App is superior to SMBP alone in terms of blood pressure reduction and improved drug adherence in patients with hypertension.
Abstract 11770: Cost-Effectiveness Analysis of Coronary Artery Disease Screening in Patients With Breast Cancer
Authors: Ragani Velusamy, Mark Nolan
Journal: Circulation (2022)

Background: Association of cardiovascular disease with cancer is caused by an increased risk of coronary artery disease (CAD), in part attributable to the association of standard risk factors with both coronary disease and cancer. In addition to these drivers of accelerated plaque formation, treatment used in breast cancer therapy is associated with CAD. Purpose: Cancer patients require an individualised approach for managing CAD and there is an unmet need to define the benefit of CAD screening on outcomes in cancer survivors and the cost-effectiveness of this approach is unknown. Methods: A Markov model was assembled using three states; well, myocardial infarction and death. Base case scenario was a 55 year old female treated for breast cancer, followed up 10 years post treatment. Costs, utilities, and transition probabilities were derived from published literature. Costs are in 2021 AUD$ and calculated from a societal perspective. Costs and utilities were discounted at 3% per annum. Sensitivity analyses were performed on key inputs including transition probabilities of well state and MI, costs of CAD and screening test. Willing-to-pay threshold of AUD$50,000 was selected. Results: Screening cancer survivors for CAD dominated no screening, providing cost savings of $1916 and QALY savings of 5.9 QALYs per-patient. Major determinants were probabilities of MI, death and costs of screening and MI. There was no change in life expectancy. Conclusion: Screening for CAD provided an increase in long-term QALY and reduction in healthcare costs in breast cancer survivors at least 10 years post treatment. ​
Abstract 12473: Assessing Disease Severity Using Machine-Learning of Baseline 12-Lead Ecg Parameters in Attr Cardiac Amyloidosis
Authors: Dominic Pimenta, Jorg Taubel, Martin Anyim, Julian D Gillmore, Tingting Zhu, Tamer Rezk
Journal: Circulation (2022)

Introduction: Cardiac amyloidosis accounts for 13% of all patients with heart failure with preserved ejection fraction (HFpEF). The National Amyloidosis Centre (NAC) scoring system (Stage 1-3), utilising eGFR and NT-proBNP correlates well with overall prognosis. Hypothesis: We wished to explore the feasibility of diagnosing disease severity using 12-lead ECG alone, using our database of &gt;6,000 ECGs from 292 ATTR patients. Methods: Triplicate 12-lead ECG parameters (PR interval, QRS width, QT-interval, QRS morphology, axis, rhythm and low amplitude presence or absence), baseline NT-proBNP and baseline eGFR were extracted. Patients with pacing were excluded. For numeric baseline parameters, the mean triplicate ECG value was used. NAC stage was then calculated from eGFR and NT-proBNP (Stage 1: NT-proBNP &lt;3000 AND eGFR &gt;45, Stage 3: NT-proBNP &gt;3000 and eGFR &lt;45, Stage 2: meets neither stage 1 or 3 criteria). Data was assembled (Excel) and then machine learning models (multilayer perceptron, decision tree (DT), naïve bayes (NB), support vector machine and radius neighbours) were trained in a 80:20 split, with 5-fold stratified cross-validation (sklearn, Python 3.0) performed on the training set for tuning of hyperparameters, and the final model output performance measured on the separate test set. Performance was measured by F1 score. Results: 295 patients were originally included, and 37 were excluded due to pacing, leaving 258 patients in the final dataset. On cross-validation the NB classifier performed best (F1 average 0.6) and the worst performing model was DT (F1 average 0.52). On the final test set the NB model performed as follows: Stage 1 NAC = F1 score 0.7, Stage 2 NAC = F1 score 0.45, Stage 3 NAC = F1 score 0.0. Conclusions: Despite the small dataset size, a machine learning approach could detect stage 1 disease with reasonable accuracy but struggled to differentiate between stage 2 and 3 disease. This model requires further external validation. We have demonstrated it is feasible to use a 12-lead ECG alone to diagnose stage 1 disease severity in ATTR-CM but not more advanced disease using machine learning.
Abstract 12322: Red Meat Consumption and The Risk of Cardiovascular Diseases and Diabetes: A Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials
Authors: Wenming Shi, Xin Huang, C Mary Sching, Jie Zhao
Journal: Circulation (2022)

Introduction: Observational studies show inconsistent associations of red meat consumption with cardiovascular disease (CVD) and diabetes. Moreover, red meat consumption varies by sex, whether the associations vary by sex remains unclear. Methods: This systematic review and meta-analysis was performed to summarize the evidence concerning the association of unprocessed and processed red meat consumption with CVD, coronary heart disease (CHD), stroke, type 2 diabetes (T2DM), and gestational diabetes mellitus (GDM). Two researchers independently searched PubMed, Web of Science, Embase, and the Cochrane Library for observational studies and randomized controlled trials (RCTs) published before September 2021. Results: A total of 44 observational studies (N=4,857,244) for CVD and 28 observational studies (N=1,897,591) for diabetes were included. Red meat consumption was positively associated with risk of CVD [relative risk (RR) 1.11, 95% confidence interval (CI) 1.05 to 1.17 for unprocessed red meat; RR 1.15, 95% CI 1.09 to 1.22) for processed red meat], CHD and stroke, with no clear sex disparity. Both unprocessed and processed red meat consumption were related to a higher risk of T2DM, and unprocessed red meat consumption was related to risk of GDM. The associations with T2DM were more evident in men than in women, and in western countries. Conclusions: Our study suggests that unprocessed and processed red meat consumption are both associated with higher risk of CVD, CHD, stroke, and diabetes, with a more obvious association in women for diabetes. These findings highlight the need for a better understanding of the mechanisms to facilitate improving cardiometabolic health.
Abstract 11617: Chronic Spinal Cord Stimulation Mitigates Cardiac Sympathoexcitation and Reduces Ventricular Arrhythmias Induced by Myocardial Infarction
Authors: Yuki Kuwabara, Siamak Salavatian, Kimberly Howard-Quijano, Aman Mahajan
Journal: Circulation (2022)

Introduction: Spinal cord stimulation (SCS) is effective neuromodulation therapy for pain, but little is known about the effectiveness of SCS for arrhythmia prevention in chronic myocardial infarction (MI). Hypothesis: Chronic SCS reduces MI-induced cardiac sympathoexcitation and reduces ventricular arrhythmias. Methods: Yorkshire pigs were randomized to chronic left circumflex coronary artery MI alone (n=11) or MI + chronic SCS (n=9). Epidural SCS lead was placed percutaneously T1-T4 of the spinal cord and reactive SCS was performed at 10 kHz, 0.03ms, and 2.5mA after MI. Holter ECG was recorded for heart rate variability (HRV) analysis, performed throughout 4-5 weeks post-MI. To create acute stress in chronic MI, epicardial extraventricular programmed stimulus (S1/S2 pacing), and acute left anterior descending coronary artery (LAD) ischemia(1h)+reperfusion(2h) (I/R) injury were conducted during terminal experiment. SCS was continued throughout terminal experiment. Cardiac electrophysiological data (activation recovery interval (ARI) and dispersion of repolarization (DOR)), as well as ventricular arrhythmia quantification were measured by placing a 56-electrode mesh sock over the heart . Data is shown as mean±SEM. Results: 1 week after MI, 30min HRV showed a higher high-frequency band and lower very-low and low-frequency band with SCS (%HF: MI 25±4 vs SCS 51±4, p=0.0028. %VLF: 50±4 vs 30±3, p=0.0015. %LF: 22±2 vs 14±2, p=0.047). In the terminal experiment, SCS reduced the maximum slope (Smax) of the electrical restitution curve described by S1/S2 pacing (Smax: MI 0.6±0.03 vs SCS 0.4±0.05, p=0.023). After acute LAD ischemia, SCS reduced global %ARI change (MI -19±3% vs SCS -11±1%, p=0.019), specifically in the ischemic region (MI -31±4% vs SCS -16±3%, p=0.008), and global %DOR (MI 1513±288% vs SCS 595±144%, p=0.011). Chronic SCS also reduced ventricular tachycardia and ventricular fibrillation during acute I/R (MI 15±3 vs SCS 5±0.8, p=0.014). Conclusions: Reactive SCS therapy mitigates cardiac autonomic imbalance in chronic MI and protects from new acute ischemia induced cardiac sympathoexcitation and ventricular arrhythmias.
Abstract 11620: Time Course of Pericardial Effusion After Catheter-Free Ventricular Ablation With Proton Beam in Swine Normal Heart
Authors: Tatsuhiko Hirao, Kimitake Imamura, Atsushi SUZUKI, Maryam E Rettmann, Omar Z Yasin, N Gurukripa N Kowlgi, Stephan Hohmann, Hiroki Konishi, Naoto Otsuka, Douglas L Packer, Alexa Miller
Journal: Circulation (2022)

Background: Cardiac proton beam ablation therapy has emerged as a promising tool for catheter-free arrhythmia ablation. The time course of the lesion change was demonstrated in MRI 8 weeks following the ablation; however, the pericardial effusion after the ablation has not been fully analyzed. Objective: The purpose of this study was to evaluate the pericardial effusion after pencil-beam scanned proton therapy on normal myocardium in swine in MRI. Methods: 32 domestic swine were irradiated with pencil-beam scanned proton therapy using irradiation doses of 30/40Gy to the left ventricle (LV) anterior wall, posterior wall, and apex. Each swine was subjected to monthly contrast-enhanced cardiac MRI to evaluate the post-irradiation effects. Results: Moderate to significant pericardial effusion (PE) was observed in 10 swine (31%), starting at 4 weeks, and increasing from 8-16 weeks until 24 weeks. With the exception of one case,, improvement was observed in all animals within a month from when the PE first became moderate or significant. . In the case where the significant PE did not improve, the PE was non-septic and transudate. Clinically, the PE did not cause cardiac tamponade and did not correlate to sudden death. Also, there was no correlation between animals with larger tissue volumes receiving higher dose (more than 20Gy) and the grade of PE . Conclusion: Proton beam radiation caused various grades of pericardial effusion, but in 90% of the animals, it resolved without intervention within a month with no major adverse events.
Abstract 12592: Nuclear Sirtuin Sirt6, Protects Mice From Endotoxin-Induced Septic Cardiomyopathy
Authors: Sadhana A Samant, Vinod Kumar Bhaskara Pillai, Samantha Hund, Madhu Gupta, Mahesh P Gupta
Journal: Circulation (2022)

Introduction: Dysregulated systemic inflammatory response from host to infection can result in sepsis and multi-organ failure. Heart is one of the most affected organ. Even with recent medical advances, mortality rate with sepsis is 30-70%. Imbalance of inflammatory and metabolic pathways are crucial in the pathogenesis of sepsis and a multi-target approach is needed. SIRT6 is a key enzyme shown to restore energy homeostasis and to promote cardiac health in various adverse conditions. Hypothesis: We examined whether SIRT6 could alleviate pathogenic effects of sepsis in a murine lipopolysaccharide (LPS)-induced cardiomyopathy model. Methods: By injecting 10mg/kg LPS in wild-type (WT) and SIRT6 whole body overexpressing (T6-Tg) mice, endotoxemia was induced (n=5-6 each). Cardiac functions were assessed by echocardiography. Using heart tissues (n=3 each), TaqMan gene expression arrays were analyzed. Heart protein and serum cytokine levels were also estimated. Rat H9C2 cell line was used for in vitro studies. Results: SIRT6 overexpression in mice prevented LPS-induced hypothermia (p&lt;0.001) and limited mortality to 30% compared to WT. LPS-injected T6-Tg mice showed preserved cardiac functions compared to WT (fractional shortening and ejection fraction, p&lt;0.001). LPS-injected WT mice hearts showed 2- to 6-fold mRNA upregulation in pro-inflammatory transcription factors HIF1α, TLR4 and activating transcription factor 4 (ATF4). These factors were significantly (p&lt;0.05) downregulated in LPS-injected T6-Tg hearts. With four-fold increase in ATF4 mRNA, a known inducer of amino acid transporters, expression of solute carriers (SLC3a2/7a1/7a5/7a8) was significantly upregulated in LPS-treated WT hearts, while reduced with SIRT6 overexpression. Pyruvate dehydrogenase kinase 4, which controls metabolic switch in sepsis, showed 4-fold increase in mRNA expression in LPS-treated H9C2 cells that was downregulated by SIRT6 overexpression. Similarly, upregulated inflammatory cytokines IL6, TNFα and lipocalin-2 were significantly (p&lt;0.05) downregulated with SIRT6 overexpression. Conclusion: Our results indicate that SIRT6 could protect heart from LPS-induced sepsis by restoring metabolic homeostasis via regulation of multiple pathways.
Abstract 12304: Right Ventricular Hemodynamics in COVID Patients With Shock
Authors: Steven M Hollenberg, Joseph E Parrillo, Brent Klinkhammer, Sameer Jamal, David Landers, Lucy M Safi, Jana Tancredi, Zoltan Turi
Journal: Circulation (2022)

Introduction: Patients with serious COVID infections frequently develop shock. Their right-sided hemodynamic profiles have not been well characterized. Methods: In a prospectively collected database including 1997 patients hospitalized for COVID pneumonia from March 2020 to March 2021, 368 had shock requiring vasopressors. 327 had echocardiography to assess ventricular function and stroke volume based on clinical indications. LVEF (LV ejection fraction) and RVFAC (RV fractional area change) were measured using Simpson’s rule, stroke volume (SV) by aortic Doppler, and RVSP (RV systolic pressure) from tricuspid regurgitation velocity; 187 had evaluable data on all parameters. Patients were divided into groups with low or preserved RVFAC ( RVFAC L or RVFAC P , cutoff &amp;lte35%), and low or normal cardiac index, (CI, CI L or CI N , cutoff &amp;lte2.2 L/min/m 2 ). Results: Mean age: 65±12, LVEF 59.5±12.8, RVFAC 35.3±10.6, CI 2.41±0.89. Overall hospital mortality in this cohort with shock was 80%. Mean RVSP was 38.8±12.2, PEEP 11.0±3.7. 43% of patients had low RVFAC (&amp;lt35%), and RVFAC correlated with other measures of RV function such as tricuspid annular peak systolic excursion (TAPSE) and lateral tricuspid annulus peak systolic velocity (S’). Higher RVSP correlated with lower CI (r=0.134, p= 0.016) but not with PEEP (r=0.03, p=0.70). Mortality did not differ significantly among groups, (p=0.19 by ANOVA) but was highest in the group with low RVFAC and low CI. ( Figure ) Conclusion: RV dysfunction is common in patients with severe COVID-19 and shock. Although RV dysfunction is probably associated with a worse prognosis, outcome in COVID may be tied to pulmonary recovery. Whether treatment targeted at RV dysfunction will improve outcome remains uncertain.